Abstract
Background: The etiology and pathogenesis of odontogenic lesions remain to be determined. Previous studies have identified epigenetic and genetic alterations that may be relevant to lesions progression and development. Hypermethylation of the Ras association domain family protein 1A (RASSF1A) has been observed in a variety of human cancers. However, the methylation status of RASSF1A in odontogenic lesions remains unknown. Thus, the aim of this study was to investigate the prevalence of RASSFA promoter hypermethylation and v-raf murine sarcoma viral oncogene homolog B V600E mutant (BRAF V600E) expression as well as the correlations between these alterations and clinicopathological features of patients with odontogenic lesions. Methods: We subjected 66 formalin-fixed, paraffin-embedded odontogenic lesions [ameloblastoma (AM), 21; ameloblastic carcinoma (AC), 6; odontogenic keratocyst (OKC), 19; and dentigerous cyst (DC), 20] to methylation-specific polymerase chain reaction to determine RASSF1A hypermethylation and immunohistochemistry to detect BRAF V600E protein expression. Results: We observed RASSF1A hypermethylation in 20% (4/20; methylation could not be detected in one lesion), 100% (6/6), 26.3% (5/19), and 5% (1/20) of AM, AC, OKC, and DC samples, respectively. RASSF1A methylation was significantly more frequently observed in AC relative to AM, OKC, and DC (p
Highlights
Odontogenic tumors and cysts are a heterogeneous group of diseases derived from the cells of the tooth forming apparatus and their remnants [1] [2]
Concomitant Ras association domain family protein 1A (RASSF1A) methylation and positive BRAF V600E expression are commonly observed in ameloblastic carcinoma (AC), which may contribute to AC tumorigenesis
We investigated the potential correlations of the RASSF1A promoter methylation status and BRAF V600E immunohistochemical expression with various clinicopathological characteristics in AM, AC, Odontogenic keratocysts (OKCs), and dentigerous cysts (DCs) samples
Summary
Odontogenic tumors and cysts are a heterogeneous group of diseases derived from the cells of the tooth forming apparatus and their remnants [1] [2]. The aim of this study was to investigate the prevalence of RASSFA promoter hypermethylation and v-raf murine sarcoma viral oncogene homolog B V600E mutant (BRAF V600E) expression as well as the correlations between these alterations and clinicopathological features of patients with odontogenic lesions. Methods: We subjected 66 formalin-fixed, paraffin-embedded odontogenic lesions [ameloblastoma (AM), 21; ameloblastic carcinoma (AC), 6; odontogenic keratocyst (OKC), 19; and dentigerous cyst (DC), 20] to methylation-specific polymerase chain reaction to determine RASSF1A hypermethylation and immunohistochemistry to detect BRAF V600E protein expression. Results: We observed RASSF1A hypermethylation in 20% (4/20; methylation could not be detected in one lesion), 100% (6/6), 26.3% (5/19), and 5% (1/20) of AM, AC, OKC, and DC samples, respectively. No correlations of RASSF1A methylation and BRAF V600E expression with clinicopathological features were observed. Conclusions: Concomitant RASSF1A methylation and positive BRAF V600E expression are commonly observed in AC, which may contribute to AC tumorigenesis
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